Mycophenolate-Based Therapy for Kidney Transplant Recipients Without HLA-DQ Mismatch

NCT ID: NCT06493526

Last Updated: 2024-08-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-20
• Study Completion Date: 2027-06-30

Brief Summary

The goal of this clinical trial is to learn if calcineurin-inhibitor therapy (a drug commonly used to prevent rejection) can be safely stopped in kidney transplant recipients with a relatively low risk of rejection (being recipients of a first transplant, without any signs of pre-existing immunity against the graft, and having a good HLA match with the donor (no mismatch in HLA-DQ)). Before stopping the calcineurin-inhibitors, the remaining therapy with mycophenolate mofetil and corticosteroids will be optimized.The main questions it aims to answer are:

Is this approach safe, in terms of preventing rejection? Is this approach well tolerated? Will this approach lead to better kidney function and/or other beneficial effects?

Detailed Description

In summary, this pilot, prospective, single-arm open interventional study the investigators will include immune-quiescent zero-DQ mismatched kidney transplant recipients between 3-12 months post-transplant who are on a CNI-based regimen with corticosteroids and MMF. After optimization of MMF dose, targeted at an MPA AUC12 of 60 (±15) mg.h/L, CNIs will be tapered and stopped over a 4 week peri-od. Prednisolon dose will be temporarily increased to 10 mg/day at the day of CNI withdrawal for 14 days, and continued at 5 mg/d thereafter. The primary outcome is biopsy-proven rejection at 6 months after CNI withdrawal. Secondary outcomes will look at other markers of alloreactivity (dnD-SA without clinical or histological signs of rejection), tolerability of MMF in the defined range, infec-tious complications, and possible favorable effects of CNI withdrawal (on GFR, tubular function, blood pressure, lipid profile and diabetes).

Conditions

Kidney Transplantation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Withdrawal of calcineurin-inhibitors in zero-HLA DQ-mismatched kidney transplant recipients

calcineurin-inhibitor withdrawal, continue on a concentration controlled mycophenolate dose (AUC12 target 60 h.mg/L)

Group Type: EXPERIMENTAL

Withdrawal of calcineurin-inhibitor, continue on concentration-controlled mycophenolate mofetil and corticosteroids.

Intervention Type: DRUG

Mycophenolate mofetil dose will be optimized to an AUC12 of 60 h.mg/L, thereafter the calcineurin inhibitor will be withdrawn.

Interventions

Withdrawal of calcineurin-inhibitor, continue on concentration-controlled mycophenolate mofetil and corticosteroids.

Mycophenolate mofetil dose will be optimized to an AUC12 of 60 h.mg/L, thereafter the calcineurin inhibitor will be withdrawn.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

• Adults ≥ 18 years old who received a first, zero-HLA-DQ mismatched kidney transplant between 3 and 12 months before screening. ((mis)matching based on the broad Eurotransplant Match determinant for DQA1 and on the split Eurotransplant Match determinant for DQB1
• Maintenance immunosuppressive therapy should consist of a calcineurin-inhibitor (tacrolimus or cyclosporine), MMF and corticosteroids
• subjects capable of giving informed consent
• eGFR ≥ 20 ml/min/1.73m² based on CKD-EPI Creatinine-Cystatin Equation at screening
• Recent HLA antibody testing (<6 weeks before screening)
• Absence of DSA (MFI > 500) at screening and in all historical samples
• Absence of subclinical rejection on a protocol kidney transplant biopsy according to latest Banff criteria (excl. borderline lesions)
• Recent assessment of CNI and MPA AUC (performed at least 8 weeks after transplantation, but <12 weeks before screening, )
• Recent OGTT in patients not on antidiabetic therapy (<3 months ago)

Exclusion Criteria

• Receipt of a non-renal transplant
• HLA identical sibling donor transplant
• ABO incompatible kidney transplantation
• cdc-PRA at transplantation > 50%
• Ongoing treatment with immunosuppressive drugs other than CNI, MMF/MPA and cortico-steroids
• Prophylactic therapy with valganciclovir
• History of biopsy-proven acute rejection
• Unexplained rise in creatininemia >20% over the last 6 weeks
• Albuminuria > 1g/day ( based on latest 24h urine collection max 6 weeks ago)
• Chronic diarrhea or gastrointestinal disorders that interfere with the absorption or oral medi-cation
• Active peptic ulcer disease
• Active hepatitis B, hepatitis C or human immunodeficiency virus infection at the day of trans-plantation
• New diagnosis of malignancy since transplantation, except successfully treated nonmetastatic basal or squamous cell carcinoma of the skin
• Pregnancy or lactation
• Patients unwilling to use reliable anticonception during the study (Male patients or their untreated female partner must use reliable contraception during my-cophenolate treatment and for at least 90 days after stopping MMF treatment. Female patients who can get pregnant must use at least one reliable form of contraception before, during and for 6 weeks after stopping MMF treatment)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Antwerp

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rachel Hellemans, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Antwerp University Hospital, Department of Nephrology, Drie Eikenstraat 655, 2650 Edegem, BELGIUM

Hans de Fijter, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Antwerp University Hospital, Department of Nephrology, Drie Eikenstraat 655, 2650 Edegem, BELGIUM

Locations

University Hospital Antwerp

Edegem, Antwerp, Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Rachel Hellemans, MD PhD

Role: CONTACT

rachel.hellemans@uza.be

+3238213435

Hans de Fijter, MD PhD

Role: CONTACT

nefrologie@uza.be

+3238213435

Facility Contacts

Rachel Hellemans, MD PhD

Role: primary

rachel.hellemans@uza.be

+3238213435

Other Identifiers

UZA-6402

Identifier Type: -

Identifier Source: org_study_id